Optimization of Lead Compounds
Since many lead compounds that are sufficiently potent in-vitro struggle to meet candidate nomination requirements due to poor pharmacokinetics, it is often important to evaluate the structural modifications that can improve the overall candidacy of a compound. The key at this stage is to identify the best potential modifications before synthesizing the compounds. This can be done by predicting physical properties of proposed synthetic analogs, and evaluating trends to make informed decisions on which modifications present higher likelihoods of success. This approach narrows the focus to a smaller set of compounds and eliminates unnecessary synthetic efforts.
Identify Suitable Substituents to Achieve Desired ADME Characteristics
Do you struggle when trying to optimize your most potent lead compounds for bioavailability? Do you find that project teams cannot preserve potency when optimizing for solubility? With the new ACD/Structure Design Suite software, ACD/Labs provides a convenient design studio for medicinal and development chemists focusing on the ability to improve drug-like properties of their lead compounds by helping them quickly evaluate possible structural modifications. The software suggests structural analogs with the desired molecular physical properties and selected ADME characteristics, while preserving the identified pharmacophore, and substantially simplifies the selection process.
ACD/Structure Design Suite includes databases of substituents that serve as an ideal brainstorming tool for identifying elementary and creative functional groups, helping shift physical properties of your lead compound in favorable directions. Your own libraries can also be included.
Often simple rearrangements of heteroatoms within ring systems can achieve design goals set out in the working hypothesis, but it may be difficult to specify which heterocycles, and at which points of attachment. The database of heterocycles within Structure Design Suite catalogs the anticipated properties of every possible 5-member, 6-member, 5,6-fused, and 6,6-fused heterocycle according to every position of attachment.
Understand the Relationship Between Structure and Property
The calculation protocols reported in ACD/pKa DB and ACD/LogP DB (also included with ACD/Structure Design Suite) give critical insight into the relationship between structure and properties. Hammett equations for pKa and fragment contributions for logP provide a framework strategy for considering structural modifications and substituents selection.
Given 30 minutes of ACD/Structure Design Suite research, an entire week of synthetic effort can be focused into a direction likely to improve the drug-like properties of your lead series.
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